Targeted delivery of anti-cancer agents to tumor tissue, with minimum damage to normal cells and tissue, is an important goal in cancer therapy. Cancer nanotechnology platforms have shown promise. However, an important consideration for effective drug delivery is precise spatial and temporal release of therapeutic agents at the target site. The development of on-demand drug release (triggering) approaches is based on utilization of either abnormal biology of the tumors (internal) or the unique physical properties of the nanoparticles (external trigger). In the liposome field, various triggering modalities used in the past include local hyperthermia, use of metal ions, pH, enzymes and light (radiation) (Torchilin et al., Nat. Rev. Drug. Discov. 2005, 4, 145-160; Andresen et al., Prog. Lipid Res. 2005, 44, 68-97).
Liposomes include a lipid bilayer wall surrounding a cavity. A molecule, such as a bioactive agent, can be encapsulated within the cavity. If the lipid bilayer is disrupted, the bioactive agent may be released from the cavity. Disruption can occur when a conformational change in one or more lipids in the lipid bilayer is induced, thereby destabilizing the lipid bilayer. One mechanism for disruption is photo-triggering. Light-sensitive liposomes have been studied since the early 1980s. When a light-sensitive liposome is exposed to light, the liposome's lipid bilayer is disrupted and an agent within the liposomal cavity can be released. The principle(s) of photo-triggering include photopolymerization of lipids (Regen et al., Biochem. Biophys. Res. Commun. 1981, 101, 131-136), photosensitization by membrane anchored hydrophobic probes (Bisby et al., BBRC 2000, 276, 169-173; Chandra et al., Org. Biomol. Chem. 2006, 4, 1730-1740; Lavi et al., Biophys. J. 2002, 82, 2102-2110), or photoisomerization of photoreactive lipids (Morgan et al., FEBS Lett. 1995, 375, 113-116). Most photo-triggerable liposomes require ultraviolet light radiation to disrupt the lipid bilayer. Ultraviolet light triggering, however, is unsuitable for in vivo applications since UV light cannot penetrate tissue to a sufficient depth to be effective. Thus, there is a need for liposomes that are responsive to tissue-penetrating wavelengths for “on-demand” drug release in vivo.